'The role of GABA signalling in the electrical timekeeping of the master circadian clock to drive circadian rhythms'

“我们的日常或昼夜生物钟是我们身体中最重要的定时系统之一，确保我们的大脑活动与我们全天的体内平衡、生理和行为需求适当地保持一致。”这包括我们睡眠-觉醒周期的时间、认知能力的峰值和代谢活动。这种日常节奏的中断可能导致严重的健康后果，包括早衰和精神健康障碍。在哺乳动物中，主生物钟位于下丘脑视交叉上核（SCN）。在SCN中，时钟基因的活动在SCN神经元中产生每日兴奋性节律，导致它们在细胞内钙含量高的白天以更高的速率激增，而在细胞内钙含量低的夜间活动较少。这种基因表达和电活动的日常节奏对生物钟功能至关重要，有助于促进身心健康。GABA是SCN中的主要神经递质，对昼夜节律bb0的产生至关重要。值得注意的是，尽管SCN中的GABA能信号对我们的日常节奏感至关重要，但GABA信号如何调节SCN的电和细胞内钙活性仍然知之甚少。”

"Our daily or circadian body clock is one of the most important timing systems in our body, ensuring that our brain activity is appropriately aligned with our homeostatic, physiological, and behavioural needs across the day. This includes the timing in our sleep-wake cycle, peak cognition ability, and metabolic activity. Disruption of this daily rhythm can lead to severe health consequences, including premature ageing and mental health disorders.In mammals, the master circadian clock is located in the hypothalamic suprachiasmatic nucleus (SCN). In the SCN, the activity of clock genes produces daily excitability rhythms in SCN neurons, causing them to spike at higher rates during the day with high intracellular calcium and less active at night with low intracellular calcium [1]. This daily rhythm in gene expression and electrical activity is vital for clock function, promoting well-being and good health.GABA is the main neurotransmitter in the SCN and is critical for the generation of circadian rhythms [2]. Remarkably, although GABAergic signalling in the SCN is critical for our sense of daily rhythm, how GABA signals regulate SCN electrical and intracellular calcium activity remain poorly understood."